We propose to examine androgen induced gene expression in the mouse submaxillary gland with the aims of 1) determining whether androgen responsive genes are clustered in the mouse genome, and 2) biochemically characterizing genetically identified cis-acting loci that regulate expression of androgen inducible genes in a tissue specific manner. The advantages of this system for a combined genetic and biochemical study of the regulation of androgen induced gene expression are several: (1.) The gland synthesizes and secretes a large number of important gene products in significant amounts in response to androgen, thus permitting the biochemical characterization of the products and cloning of their corresponding mRNA sequence. These gene products include NGF (nerve growth factor), EGF (epidermal growth factor), renin, and a genetically clustered family of arginylesteroproteases. (2.) Within inbeed mouse strains, genetic polymorphism has already been identified for several of the structural loci, and for an element that regulates the androgen responsiveness of renin in a tissue specific manner. (3.) This genetic polymorphism is apparent when mRNA is translated in vitro (Preliminary Results). (4.) A large array of mouse genetic resources that include recombinant inbred strains and mouse-hamster hybrid cell lines are now available to supplement classical inbred strain resources in answering these questions. A cDNA library from submaxillary gland will be constructed and screened by a variety of approaches to identify probes fro androgen inducible genes corresponding to NGF, EGF, renin, the set of arginylesteroproteases, as well as several previously undescribed polypeptides that respond to androgen induction. These recombinant DNA probes will be used in combination with the above described genetic resources to investigate mechanisms regulating androgen induced gene expression.